A Glycosphingolipid/Caveolin-1 Signaling Complex Inhibits Motility of Human Ovarian Carcinoma Cells

Prinetti, Alessandro; Cao, Ting; Illuzzi, Giuditta; Prioni, Simona; Aureli, Massimo; Gagliano, Nicoletta; Tredici, G; Rodriguez-Menendez, Virginia; Chigorno, Vanna; Sonnino, Sandro

doi:10.1074/jbc.m111.286146

Cited by 32 publications

(19 citation statements)

References 56 publications

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“…Conversely, Src regulated caveolin-1 function through the phosphorylation of caveolin-1 [23]. Recently, Prinetti and coworkers reported that ganglioside GM3/caveolin-1 interactions are potentially important in the motility of ovarian carcinoma cells [24]. Although a correlation between increased ganglioside GM3 levels and increased caveolin-1 expression was reported, the role of GM3 in caveolin-1 oligomerization was not studied.…”

Section: Discussionmentioning

confidence: 99%

Glycosphingolipid Mediated Caveolin-1 Oligomerization

Shu

Shayman²

2012

J Glycom Lipidom

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We have previously demonstrated an association between the accumulation of the glycosphingolipid globotriaosylceramide (Gb3) and the loss of high molecular weight oligomers in the aortas of α-galactosidase A-knockout mice, a model of Fabry disease. In the present study the molecular basis for the association between glycosphingolipids and caveolin-1 oligomerization was further investigated. Cellular glycosphingolipids were selectively depleted by treatment with a series of sphingolipid synthesis inhibitors, including D-threo-ethylenedioxyphenyl-2-palmitoylamino-3-pyrrolidino-propanol, fumonisin B1 and myriocin. The depletion of glycosphingolipids resulted in the loss of high molecular mass oligomers of caveolin-1 in plasma membranes of cultured ECV-304 cells as well as in the caveolar fractions of Hela cells as measured by immunoblotting. The disruption of caveolin-1 high molecular weight oligomer formation caused by changes of composition of glycosphingolipids may be directly involved in the interruption of cellular functions including caveolar stabilization, membrane trafficking and signal transduction. These results suggest a specific role for glycosphingolipidsin the caveolar co-localization and oligomerization of caveolin-1.

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Section: Discussionmentioning

confidence: 99%

Glycosphingolipid Mediated Caveolin-1 Oligomerization

Shu

Shayman²

2012

J Glycom Lipidom

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“…Conversely, compared to wild-type cells, stable overexpression of sialyltransferase-1 (SAT-1, GM3 synthase) or pharmacological manipulation of A2780 human ovarian cancer cells with N-(4-hydroxyphenyl) retinamide had elevated ganglioside levels, reduced in vitro cell motility, and enhanced expression of the membrane adaptor protein caveolin-1 [26]. In GM3 synthase-overexpressing clones, both depletion of gangliosides by treatment with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and silencing of caveolin-1 by siRNA increased in vitro cell motility [27]. …”

Section: Discussionmentioning

confidence: 99%

Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Huang

Bijangi-Vishehsaraei

Saadatzadeh³

et al. 2012

JCT

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Background Taxol (paclitaxel) inhibits proliferation and induces apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy. Materials and Method The roles of GM3 synthase (α2,3-sialyltransferase, ST3Gal V) in attenuating Taxol-induced apoptosis and triggering drug resistance were determined by cloning and overexpressing this enzyme in the SKOV3 human ovarian cancer cell line, treating SKOV3 and the transfectants (SKOV3/GS) with Taxol and determining apoptosis, cell survival, clonogenic ability, and caspase-3 activation. Results In this report, we demonstrated that Taxol treatment resulted in apoptosis which was associated with caspase-3 activation. Taxol treatment upregulated the expression of human GM3 synthase, an enzyme that transfers a sialic acid to lactosylceramide. Moreover, we cloned the full-length GM3 synthase gene and showed for the first time that forced expression of GM3 synthase attenuated Taxol-induced apoptosis and increased resistance to Taxol in SKOV3 cells. Conclusions GM3 synthase overexpression inhibited Taxol-triggered caspase-3 activation, revealing that upregulation of GM3 synthase prevents apoptosis and hence reduces the efficacy of Taxol therapy.

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“…TACA expression can be a result of changes in several different steps in the glycoprocessing machinery, including increased/decreased sialylation 14–24 or fucosylation 25–29 , increased N-linked glycan branching, altered O-linked glycolipid (ganglioside) compositions 30–34 and truncated mucin-type O-glycans. 16,35–50 These structures, in part, may modify the physical and chemical properties of the tumor cell, leading to altered cell adhesion and signal transduction, often resulting in enhanced aggressiveness and metastatic potential.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles

Biswas

Medina

Barchi

2015

Carbohydrate Research

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The Thomsen Friedenreich antigen (TFag) disaccharide is a tumor-associated carbohydrate antigen (TACA) found primarily on carcinoma cells and rarely expressed in normal tissue. The TFag has been shown to interact with Galectin-3 (Gal-3), one in a family of β-galactoside binding proteins. Galectins have a variety of cellular functions, and Gal-3 has been shown to be the solegalectin with anti-apoptotic activity. We have previously prepared gold nanoparticles (AuNP) coated with the TFag in various presentations as potential anti-adhesive therapeutic tools or antitumor vaccine platforms. Here we describe the synthesis of TFag-glycoamino acid conjugates attached to gold nanoparticles through a combined alkane/PEG linker, where the TFag was attached to either a serine or threonine amino acid. Particles were fully characterized by a host of biophysical techniques, and along with a control particle carrying hydroxyl-terminated linker units, were evaluated in both Gal-3 positive and negative cell lines. We show that the particles bearing the saccharides selectively inhibited tumor cell growth of the Gal-3 positive cells significantly more than the Gal-3 negative cells. In addition, the threonine-attached TF particles were more potent than the serine-attached constructs. These results support the use of AuNP as antitumor therapeutic platforms, targeted against cell lines that express specific lectins that interact with TFag.

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A Glycosphingolipid/Caveolin-1 Signaling Complex Inhibits Motility of Human Ovarian Carcinoma Cells

Cited by 32 publications

References 56 publications

Glycosphingolipid Mediated Caveolin-1 Oligomerization

Glycosphingolipid Mediated Caveolin-1 Oligomerization

Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells

Synthesis and cell-selective antitumor properties of amino acid conjugated tumor-associated carbohydrate antigen-coated gold nanoparticles

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